It is estimated that over 2.2 million Americans have glaucoma and that over 130,000 are legally blind from the disease. Early, accurate diagnosis and treatment is important to prevent the progression of the disease, and loss of visual function. The National Eye Institute National Plan program objectives highlight the need to "develop improved diagnostic measures to detect optic nerve disease, progression and treatment effectiveness". The Diagnostic Innovation in Glaucoma Study (DIGS): Structural Assessment proposes to continue the longitudinal study initiated in 1995 to develop novel methods to diagnose and monitor glaucomatous changes of the optic disc and retinal nerve fiber layer (RNFL) with the most promising new optical imaging instruments: confocal scanning laser ophthalmoscopy (CSLO), scanning laser polarimetry (SLP) and optical coherence tomography (OCT). To date, this study has determined the reproducibility and diagnostic accuracy of these new techniques and has led to significant improvements in our ability to detect glaucoma. The objectives of the current proposal are to develop improved methods to 1) detect the progression of structural damage due to glaucoma, and 2) measure the rate of glaucomatous progression and its determinants, and 3) characterize the complex relationship between structural and functional change over time. Methods: This study will include at least 600 glaucoma patients and 250 healthy controls. At the end of the proposed study, over 300 patients will have >5 years of follow-up on each technique. Each subject will complete an ophthalmologic and visual field exam every 6 months. In addition, CSLO and OCT images will be obtained to measure the optic disc and, SLP and OCT images to measure the RNFL. Photographic documentation of optic disc and RNFL changes also will be evaluated and compared to the imaging techniques. This study will provide important longitudinal data to identify the most sensitive and specific methods for detecting glaucomatous changes over time. Significance: Study of this cohort will improve our ability to monitor glaucomatous change over time in clinical practice and enhance our ability to utilize structural changes of the optic disc and retinal nerve fiber layer as endpoints in clinical trials [unreadable] [unreadable]